MFSD7C switches mitochondrial ATP synthesis to thermogenesis in response to heme

Yingzhong Li, Nikola A. Ivica, Ting Dong, Dimitrios P. Papageorgiou, Yanpu He, Douglas R. Brown, Marianna Kleyman, Guangan Hu, Walter W. Chen, Lucas B. Sullivan, Amanda Del Rosario, Paula T. Hammond, Matthew G. Vander Heiden and Jianzhu Chen ()
Additional contact information
Yingzhong Li: Massachusetts Institute of Technology
Nikola A. Ivica: Massachusetts Institute of Technology
Ting Dong: Massachusetts Institute of Technology
Dimitrios P. Papageorgiou: Massachusetts Institute of Technology
Yanpu He: Massachusetts Institute of Technology
Douglas R. Brown: Massachusetts Institute of Technology
Marianna Kleyman: Massachusetts Institute of Technology
Guangan Hu: Massachusetts Institute of Technology
Walter W. Chen: Whitehead Institute for Biomedical Research
Lucas B. Sullivan: Massachusetts Institute of Technology
Amanda Del Rosario: Massachusetts Institute of Technology
Paula T. Hammond: Massachusetts Institute of Technology
Matthew G. Vander Heiden: Massachusetts Institute of Technology
Jianzhu Chen: Massachusetts Institute of Technology

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: Abstract ATP synthesis and thermogenesis are two critical outputs of mitochondrial respiration. How these outputs are regulated to balance the cellular requirement for energy and heat is largely unknown. Here we show that major facilitator superfamily domain containing 7C (MFSD7C) uncouples mitochondrial respiration to switch ATP synthesis to thermogenesis in response to heme. When heme levels are low, MSFD7C promotes ATP synthesis by interacting with components of the electron transport chain (ETC) complexes III, IV, and V, and destabilizing sarcoendoplasmic reticulum Ca2+-ATPase 2b (SERCA2b). Upon heme binding to the N-terminal domain, MFSD7C dissociates from ETC components and SERCA2b, resulting in SERCA2b stabilization and thermogenesis. The heme-regulated switch between ATP synthesis and thermogenesis enables cells to match outputs of mitochondrial respiration to their metabolic state and nutrient supply, and represents a cell intrinsic mechanism to regulate mitochondrial energy metabolism.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-18607-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18607-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-18607-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().